New Evidence for the Mechanism of Action of a Type-2 Diabetes Drug Using a Magnetic Bead-Based Automated Biosensing Platform

The mechanism of action (MOA) of the first line type-2 diabetes drug metformin remains unclear despite its widespread usage. However, recent evidence suggests that the mitochondrial copper (Cu)-binding action of metformin may contribute toward the drug’s MOA. Here, we present a novel biosensing platform for investigating the MOA of metformin using a magnetic microbead-based agglutination assay which has allowed us to demonstrate for the first time the interaction between Cu and metformin at clinically relevant low micromolar concentrations of the drug, thus suggesting a potential pathway of metformin’s blood-glucose lowering action. In this assay, cysteine-functionalized magnetic beadswere agglutinated in the presence of Cu due to cysteine’s Cu-chelation property. Addition of clinically relevant doses of metformin resulted in disaggregation of Cu-bridged bead-clusters, whereas the effect of adding a closely related but blood-glucose neutral drug propanediimidamide (PDI) showed completely different responses to the clusters. The entire assay was integrated in an automated microfluidics platform with an advanced optical imaging unit by which we investigated these aggregation–disaggregation phenomena in a reliable, automated, and user-friendly fashion with total assay time of 17 min requiring a sample (metformin/PDI) volume of 30 μL. The marked difference of Cu-binding action between the blood-glucose lowering drug metformin and its inactive analogue PDI thus suggests that metformin’s distinctive Cu-binding properties may be required for its effect on glucose homeostasis. The novel automated platform demonstrating this novel investigation thus holds the potential to be utilized for investigating significant and sensitive molecular interactions via magnetic bead-based agglutination assay

Artificial gut-on-a-disc platform to evaluate PH sensitive coatings of oral drug delivery devices

Rapid testing of pH coatings of oral drug delivery (ODD) devices is often complex and time consuming. A lab-on-a-disc (LoD) platform was developed which enables detection of integrity of pH coatings for up to four different pHs. The platform was designed to perfuse ODD devices through different pH in a sequential manner, mimicking the pH variations in the gastrointestinal (GI) tract. The disintegration of pH coatings causes release of drugs, which in turn is used to monitor integrity of pH coatings. Combining ‘event-triggered’ flow control, based on dissolvable film with electrochemical detection, enables accelerated, real-time characterization of ODD devices

An Astigmatic Detection System for Polymeric Cantilever-based Sensors

We demonstrate the use of an astigmatic detection system (ADS) for resonance frequency identification of polymer microcantilever sensors. The ADS technology is based on a DVD optical head combined with an optical microscope (OM). The optical head has a signal bandwidth of 80 MHz, allowing thermal fluctuation measurements on cantilever beams with a subnanometer resolution. Furthermore, an external excitation can intensify the resonance amplitude, enhancing the signal- to-noise ratio. The full width at half maximum (FWHM) of the laser spot is 568 nm, which facilitates read-out on potentially submicrometer-sized cantilevers. The resonant frequency of SU-8 microcantilevers is measured by both thermal fluctuation and excited vibration measurement modes of the ADS